In contrast to the plethora of publications on placebo effects in patients, very little is known about placebo effects in healthy volunteers during clinical pharmacology studies. We therefore reviewed the adverse events spontaneously reported during placebo administration in 109 double-blind, placebo-controlled studies involving 1228 volunteers. The overall incidence of adverse events in the healthy volunteers during placebo administration was 19%. As expected, complaints were more frequent after repeated dosing (28%) and in elderly subjects (26%). Overall, the most frequent adverse events were headache (7%), drowsiness (5%), and asthenia (4%), with some variation depending on study design and population. In conclusion, these data shed new light on the impact of experimental conditions on the results of safety evaluations in healthy volunteers participating in clinical pharmacology studies.